We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Quantitative image analysis identifies pVHL as a key regulator of microtubule dynamic instability.
- Authors
Thoma, Claudio R.; Matov, Alexandre; Gutbrodt, Katrin L.; Hoerner, Christian R.; Smole, Zlatko; Krek, Wilhelm; Danuser, Gaudenz
- Abstract
Von Hippel-Lindau (VHL) tumor suppressor gene mutations predispose carriers to kidney cancer. V The protein pVHL has been shown to interact with microtubules (MTs), which is critical to cilia maintenance and mitotic spindle orientation. However, the function for pVHL in the regulation of MT dynamics is unknown. We tracked MT growth via the plus end marker EB3 (end-binding protein 3)-GFP and inferred additional parameters of MT dynamics indirectly by spatiotemporal grouping of growth tracks from live cell imaging. Our data establish pVHL as a near-optimal MT-stabilizing protein: it attenuates tubulin turnover, both during MT growth and shrinkage, inhibits catastrophe, and enhances rescue frequencies. These functions are mediated, in part, by inhibition of tubulin guanosine triphosphatase activity in vitro and at MT plus ends and along the MT lattice in vivo. Mutants connected to the VHL cancer syndrome are differentially compromised in these activities. Thus, single cell-level analysis of pVHL MT regulatory function allows new predictions for genotype to phenotype associations that deviate from the coarser clinically defined mutant classifications.
- Subjects
TUMOR suppressor genes; GENETIC mutation; RENAL cancer; PROTEINS; MICROTUBULES; CARRIER proteins
- Publication
Journal of Cell Biology, 2010, Vol 190, Issue 6, p991
- ISSN
0021-9525
- Publication type
Article
- DOI
10.1083/jcb.201006059